Follicular lymphoma and the microenvironment: potential targets and biomarkers.

Abstract

INSTRUCTION Follicular lymphoma (FL) is an indolent B cell malignancy characterized by recurrent genetic alterations, yet its clinical course is highly variable and not fully explained by tumor-intrinsic features alone. Increasing evidence highlights the tumor microenvironment (TME) as a critical regulator of disease progression, therapeutic response, and immune escape. AREAS COVERED FL TME is composed of diverse cellular elements, including T cell subsets, tumor-associated macrophages, stromal cells, and follicular dendritic cells, which collectively provide survival signals and shape immune dysfunction. These interactions have led to the identification of potential therapeutic targets, such as immune checkpoint molecules, macrophage polarization pathways, and stromal-tumor signaling axes. In parallel, microenvironment-derived biomarkers, including specific immune cell compositions, spatial organization patterns, and gene expression signatures, are emerging as important predictors of prognosis and treatment outcomes. Advances in single-cell and spatial profiling technologies have further refined our understanding of TME heterogeneity, enabling the discovery of clinically relevant targets and biomarkers. EXPERT OPINION Together, these insights support a more integrated model of FL biology and provide a foundation for developing microenvironment-directed therapies and precision medicine approaches.